Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis.
OBJECTIVE
Substance P (SP) is a vasodilator that may contribute to systemic and splanchnic vasodilatation in cirrhosis. The aim of this study was to determine the effects of SP (dose--13 pg/kg) and its specific inhibitor, RP67580 (dose--300 microg/kg) on mean arterial pressure (MAP) and portal pressure (PP) in cirrhotic rats and controls.


METHODS
MAP and PP were measured before and after administering SP and RP67580. Additionally, a small group of cirrhotic rats were pretreated with L-NAME to block the effects of nitric oxide (NO) before measurements.


RESULTS
SP produced transient systemic hypotension in both groups. SP caused a significant increase in PP in cirrhotic rats and a decrease in PP in controls. RP67580 reduced the hypotensive effect of SP, but not completely. RP67580 decreased PP in the cirrhotic group but not in controls. In cirrhotic rats pretreated with L-NAME, SP administration caused a significant decrease in MAP but no significant change in PP.


CONCLUSIONS
Exogenous SP increases PP and decreases MAP in cirrhotic rats. RP687580 decreases PP and reduces SP-induced hypotension in cirrhotic rats. NO blockade abolishes the effect of SP on PP. SP contributes to splanchnic vasodilatation in cirrhosis and this effect may be mediated by NO.
Cardenas
Andres
A
Liver Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. acardena@clinic.ub.es
Lowe
Robert
R
Oh
Sangik
S
Bodkin
Sheila
S
Kenney
Tom
T
Lamorte
Wayne W
WW
Afdhal
Nezam H
NH
D000700:Analgesics / Q000008:administration & dosage; D000758:Anesthesia / Q000379:methods*; D000818:Animals; D001706:Biopsy; D001783:Blood Flow Velocity / Q000187:drug effects* / Q000502:physiology; D002251:Carbon Tetrachloride / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D054833:Isoindoles / Q000008:administration & dosage*; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D000700:Analgesics; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D002251:Carbon Tetrachloride